Amenorrhea, Osteoporosis & Eating Disorders

By Sabina Anna Rebis

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The injuries that runners suffer from are often acute, but these acute injuries may be the result of heavy wear and tear that is sometimes secondary to self-inflicted damage due to overexercising and inappropriate nutrition. A condition that many athletes, including runners, may suffer from at some point in their lives is the athletic triad. Although first described in females as the female athletic triad, mostly because one of its three components is the loss of a menstrual cycle, two of its three components may also affect male athletes. The triad is a syndrome that consists of a pathological or unhealthy energy deficit, often due to disordered eating or overexercising without replenishing lost calories; menstrual irregularity; and bone density loss. Unfortunately, the full effect of the female athletic triad may be silent until an acute injury, such as a severe fracture, takes place, or even until menopause, when bone loss occurs at a much faster rate in those who suffered from the condition in their youth.

What is the Athletic Triad?

The female athletic triad was initially described at the early 1990’s at a meeting of the American College of Sports Medicine (ACSM) as a syndrome consisting of three components: amenorrhea, or the absence ofmenstruation, disordered eating patterns, and osteoporosis, or low bone density: the precursor to osteoporosis otherwise known as osteopenia, leading to brittle bones. Although the syndrome is known as a trifecta, having only one or two components increases long term morbidity. More recently and based on new studies, the definition of the female athletic triad has been broadened to include changes in the menstrual cycle that include all irregularities or disturbances. In addition the new definition, of Relative Energy Deﬁciency in Sport (RED-S) encompasses both male and female sufferers.

Prevalence

The prevalence of individual components of the triad in many athletes is higher than the prevalence of all three of them in just one individual. For example, secondary amenorrhea had a prevalence of 69% in women who participated in sports that emphasized body size and speed, such as gymnastics, ice skating, and running, while in comparison, the prevalence of secondary amenorrhea in the general population had only 2 – 5 %. In addition, disordered eating patterns were prevalent in 70% of professional athletes competing in sports that require weigh-ins and in 16% to 47% of female college aged elite athletes. Low bone density, either full blow bone breakdown in the form of osteoporosis or a precursor to it known as osteopenia had a prevalence of up to 50% in female athletes.

The reason why the prevalence of the disorder in athletes with all three components of the triad may be difficult to assess is because the female athlete triad can go unnoticed. Some limited studies have been able to report that all three components may be present in up to 4% of female athletes and any of the two components were found to be present in up to 27% of female athletes.

Mechanism and Causes

The loss of menstruation, significant energy deficit, and decreased bone density are all factors that are seen in those suffering from the female athletic triad. This means that more calories are consistently burned during daily physical activity and training than calories consumed, leading to the slowing of some physiological processes.

Energy Imbalance

Energy availability is the daily calorie energy intake minus daily physical activity and exercise energy expenditure. In female adults the most favorable energy availability, or the energy it takes to maintain physiology, has been defined as 45 kcal/kg per day. In adolescents who are still growing this number may be higher.

Runners and athletes who put in many miles a day, may have a negative energy balance if they under eat relative to the energy they burn. Although many athletes may be focused on increasing speed by losing pounds, many may also not be eating enough due to exhaustion, lack of time, orpurely lack of knowledge. These runners may not necessarily have disordered eating patterns, but are not taking in enough calories to sustain healthy physiology.

Those who focus on appearance and purposefully restrict calorie intake while overexercising, may fit the Diagnostic and Statistical Manual of Mental Disorders for an eating disorder or disordered eating.

When energy availability is low, the hypothalamic-pituitary-ovarian axis, a major signaling system in the body, is disturbed. Decreased gonadotropin-releasing hormone from the hypothalamus leads to decreased luteinizing hormone and follicle stimulating hormone release from the pituitary, an important signaling structure in the brain. Lack of or a decrease in luteinizing and follicle stimulating hormone is what ultimately results in irregular ovulation and menses, because of failure stimulate estrogen release and/or ovulation. Estrogen is decreased and so is calcium resorption and bone building, since estrogen plays a crucial role in both. About 30 kcal/kg of lean body mass is necessary to maintain menstrual function. Moreover studies show that increasing exercise while increasing calorie intake to maintain that number did not disrupt the hypothalamic pituitary ovarian axis.

Menstrual dysfunction

The menstrual cycle consists of phases:

The follicular phase: This is when signals from the hypothalamus tell the pituitary to release hormones that stimulate ovaries to make follicles. The lining of the uterus thickens in response to increasing hormone levels.

The ovulatory phase: The dominant follicle releases its egg for potential fertilization.

The luteal phase: The lining of the uterus that began to thicken in the follicular phase will be maintained with pregnancy or will shed if the egg is not fertilized.

The menstrual phase: The luteal phase moves to the menstrual phase and shedding of the lining, or bleeding, ensues with hormonal withdrawal.

Menstrual cycles last for 3 to 7 days and typically occur every 25-36 days on average. Disturbed menstrual cycles come in many varieties and are secondary to low or lacking hormone levels. In those with the athletic triad, these disturbances are secondary to pituitary suppression. Menstrual dysfunction includes patterns such as oligomenorrhea, amenorrhea, luteal suppression, or aovulaton.

In those with oligomenorrhea, cycles are less frequent and tend to occur over every 35 days. Secondary amenorrhea refers to the absence of a menstrual cycle for over 3 months after a period of normal menstruation. Primary amenorrhea also refers to missed cycles but in those who never began to menstruate, despite the development of the proper sexual characteristics and physiological maturation. In some cases, menstruation, or withdrawal bleeding may occur because there was enough estrogen for the uterine lining to build up, yet follicles did not mature or release their eggs due to low FSH. This is aovulation. These patterns may result in shorter or longer menstrual cycles secondary to some stimulation of the lining of the uterus from low estradiol levels, but without ovulation. In luteal suppression on the other hand, the opposite takes place: ovulation can occur, but the follicular phase is prolonged and the luteal phase, and bleeding, is shortened.

The term for menstrual dysregulaion that occurs in those with an energy deficit, or reduced calorie intake, is functional hypothalamic amenorrhea. The signaling pathway in the hypothalamic pituitary ovarian axis is thrown off due to changes in gonadotropin-releasing hormone pulsatility, resulting a in a domino effect of the disruption of lutenizing hormone release and then a disturbance in the secretion of estrogen and progesterone. Leptin, a satiety hormone, which usually has a positive effect on gonadotropin-releasing hormone secretion and regulates its’ release, is also decreased with low weight and BMI (body mass index) that may be a result of a calorie deficit and overexercise seen in patients with the female athletic triad. Leptin is secreted by adipose tissue.

Low bone density

Bone strength is combination of bone mineral content and bone turnover rates.Bones most commonly affected by low bone density include those of the lower extremities, pelvis, and vertebrae. Peak bone mass is obtained between the ages of 20 and 30 years and peak bone mineral content reached between the ages of 9 and 20 years. Bone mass begins to decline by age 30.

Mechanisms that lead to osteoporosis or osteopenosis are due to genetic and environmental factors. About half of the bone mass is accumulated during pubertal development and associated with sex hormones. By the time the end plates of the bones close, skeletal consolidation takes place and there is minimal accumulation of bone minerals.

Although the variability of bone mass, or quality of the bone architecture is determined by some genetic factors, like genes for estrogen receptors, growth factors, and collagen, bone loss is mostly determined by environmental factors, which include nutrition, behavior, and medication side effects.

Diagnosis

Diagnosis of the athletic triad is usually based on history and physical exam. The athlete should be asked about time spent in training as well as other physical activity. Eating habits and foods consumed should be assessed as well as birth control usage. The physician should ask about recent and past injuries and fractures, and about past menses including irregularities. It’s important to rule out other pathophysiological conditions that could potentially cause irregularities in menstrual cycles, such as polycystic ovarian syndrome or a thyroid disorder.

During the physical exam, the athlete may have signs that are associated with the female athletic triad. These include orthostatic hypotension, otherwise known as a significant drop in blood pressure and increase in heart rate when changing from a lying to a sitting and then standing position; bradycardia, or slow heart rate at baseline; or hypothermia with increased sensitivity to the cold and signs of poor circulation.

If the athlete admits to a history of multiple sports injuries resulting in fractures, this should indicate a need for a dual-energy x-ray absorptiometry test, known as the DXA scan. This test is used to assess bone mass density according standardized scores known as T-scores and Z-scores. While the T-score is used to predict osteoporosis and fracture risks for mostly postmenopausal woman, the Z-score can compare bone mass in an individual of any age to the average bone mass in the same sex and age group. Therefore Z-scores are a more accurate way of comparing an athlete’s bone density to a healthy individual in the same age group. Athletes with a Z-score that falls two standard deviations below the mean for their age group have low bone density that is below their expected range for age. Although the term osteopenia was used to the describe the pre-osteoporosis state, the term is no longer widely used. An athlete with a Z-score that is below the two standard deviations below the average bone mass for their age group is categorized in the osteoporosis range. This low bone density may result from a combination of nutritional deficiencies and hypoestrogenism (or a low estrogen state). A history of fractures or stress fractures is a clue that the Z-score may be below the mean. Z-scores between –1.0 and –2.0 are red flags for full blown osteoporosis.

Symptoms

Athletes with a significant energy deficit or who meet all three criteria for the female athletic triad may suffer from fainting spells, frequent headaches, and a history of stress fractures or irregular periods. They may also complain of nonspecific symptoms like vision changes or decreased appetite despite low nutritional intake. Athletes may complain of fatigue and intolerance to cold due to poor circulation in the distal extremities, or hands and feet.

Risk Factors

Risk factors for developing the athletic triad include activities that emphasize leanness, lightness, and speed. These include sports like gymnastics, diving, figure skating, aerobics, and running, or dance such as ballet. The activities that may put men at risk for the conditioninclude wrestling, rowing, or martial arts.

Complications of the Athletic Triad

In females, consequences of the triad may include infertility since hormone levels may be too low to maintain a pregnancy, if one was too occur. Low hormone levels also may lead to a lack of follicular development and ovulation. On the other hand of the spectrum, unexpected or premature ovulation might occur in those who may be starting the path to recovery from the triad, since the hypothalamic pituitary gonadal axis is regaining function leading to variation in pulsatile hormone release.

Since estrogen is also cardioprotective in women (it prevents build-up of fatty molecules in the blood that lead to high blood pressure and heart disease), low levels of estrogen can cause blood vessel wall dysfunction and propensity for fatty deposits on the walls of the vessels. Furthermore low calorie intake and nutritional status may lead to an impaired function of the immune system, increasing the frequency of colds and other illnesses.

Skeletal demineralization and a decrease in peak skeletal bone mass density occur slowly over time. Athletes with amenorrhea and low bone density have 2 to 4 times greater risk for stress fractures. Although bone building is still occurring in younger athletes who may be suffering from the athletic triad, bone mass density may improve during recovery, but may not fully “catch up” to what it would normally be had the athlete not had the condition.

Muscles, tendons, and ligaments also suffer. Tissue repair depends on proper nutrition and enough calories, and recovery in athletes who are undernourished is incomplete and takes a much longer time. Mood changes, depression, anxiety, changes in thinking, concentration, and focus may also be consequences of the triad.

Parallel Athletic Triad in Men

Studies have recently addressed the male variation of the triad. Lower testosterone levels were found in male runners exceeding 100 km/week. Reductions of testosterone were found up to 40% and reduction of sperm counts up to 43% after overtraining, as compared to baseline values. Testosterone levels did return to baseline, however, after resumption of normal training.

In endurance athletes testosterone levels declined by 12 % when training occurred between 1 and 2 hoursper day for 6–7 days per week, but values continued to remain in the physiological range.

Suppression of the hypothalamic pituitary gonadal axis also happens in male athletes which is what likely leads to reduced testosterone levels. Some runners, due to this, might resort to natural testosterone boosters supplements or testosterone increasing foods. Calorie reductions that result in energy deficits also suppress testosterone production and reduce leptin production in men. Administration of recombinant leptin during a fast in men preserved the hypothalamic pituitary gonadal function andLH pulsatility and testosterone concentrations, as it did in women.

When changes in metabolic markers associated with bone turnover were assessed, including insulin-like growth factor (IGF)-1, triiodothyronine (T3), and other bone turnover markers in men, the changes were less pronounced than in women.

Bone density may be lower in men who participate in sports emphasizing leanness, like in male jockeys. In collegiate runners, low BMI were associated with impaired lumbar bone density. However free and total estradiol were more predictive than testosterone in bone density replenishment in males. Runners subjected to energy restriction had a 15 % reduction in one type of collagen and a 17 % decrement in the insulin growth factor. Therefore, energy balance is key in maintaining bone health in men as well.

Low energy availability may be less common in male athletes and subtle changes may be even less pronounced in those suffering from energy deficits in the male population. Lower levels of sex hormones in male athletes are primarily observed in those in endurance sports. Testosterone and estrogen values outside of the normal range go hand in hand with impaired bone health. Like in women mechanical forces may help with maintenance of bone densitywhen hormone levels are lacking.

Redefining the female athletic triad

The International Olympic Committee proposed a new term for the condition: the ’‘Relative Energy Deﬁciency in Sport (RED-S)’’ to encompass both sexes and highlight the inﬂuence of inadequate nutrition on health. The syndrome of RED-S includes impaired bone health and protein synthesis in tissue regeneration, impaired metabolic rate, irregular menstrual function in females, decreased immunity, and consequently an impact on cardiovascular health caused by relative energy deficiency. According to the proposed definition, psychological consequences are associated with RED-S and can either precede or be the result of the sequelae.

The ‘Sport Risk Assessment and Return to Play Model’ contains three groups. The new model for assessment of risk injury and return to play categorizes the syndrome into three categories: red (high risk), Yellow (moderate risk), and green (low risk). The athlete’s risk should be evaluated every one to three months based on these categories.

Athletes who meet the criteria for the high risk red category are discouraged from a return to play and need to be cleared medically before adequate training can restart. Written contracts upon return to play after medical clearance should establish that the athlete or runner will maintain a certain positive energy balance and comply with medical optimization. Athletes or runners can then move on to the yellow, or moderate risk category, and begin competing once medically cleared and may return to training as long as they comply with the treatment plan. Athletes in the green, or low risk category are considered in recovery and may return to full sport participation.

Treatment

Early recognition of the athletic triad is key to treatment. Athletes suffering from the condition may initially deny that there is a problem, but medical attention is mandatory if athletes show classic signs associated with the female athletic triad. Treatment consists of a team based approach, including a physician, a psychologist or social worker, and a nutritionist. Support from team coaches, family, and those directly involved with the athlete’s training is also key in the recovery process.

A multidisciplinary treatment approach should be tailored individually because there is such a high variability in physiology and other physical characteristics in athletes, even within the same sport. It is vital to remember to maintain a positive energy balance when designing individual training programs for athletes.

The first goal of recovery should be to begin to restore the energy deficit and reverse menstrual irregularities and bone breakdown through diet and exercise modification. Since luteinizing hormone pulsatility is disrupted when caloric intake is restricted to < 30 kcal/kg fat-free mass per day, athletes may need to increase energy availability to at least this number for the return of menses to occur. The initial increase in body weight that occurs with modification of nutritional intake and exercise habits is not immediate. It may take weeks and months for a menstrual cycle to return to normal and even this will not always reverse bone damage.

Other methods of treatment, such as the use of oral contraceptive pills, may be necessary to restore menses. Many oral contraceptives contain a combination of estrogen and progestin and may help with bone restoration. However, oral contraceptives can give a false sense of recovery because menstrual bleeding resumes with the extraneous hormonal therapy, without changes in the energy deficit in the athlete.

Some studies noted that other forms of estrogen and progestin delivery, such as transdermal patches, may be more effective at improving bone density than oral contraceptives, but the most recent research has discounted that theory. The thought was that oral estrogen decreases insulin-like growth factor 1, a bone trophic hormone essential for bone remodeling, while transdermal estrogen has a minimal effect and may maintain or increase the growth factor concentrations. Generally, however, estrogen-containing contraceptives should not be used just for the purpose of increasing bone density.

Another important factor of treatment is optimizing calcium and vitamin D intake and absorption. The current daily nutritional calcium recommendation for adolescents is 1300 mg and vitamin D recommendation is 600 IU, while for premenopausal women this recommendation is 1000 mg and 600 IU, respectively.

There has been stipulation whether drugs used in postmenopausal women suffering from osteoporosis may be potentially useful in young athletes experiencing loss of bone density. However, these drugs or bisphosphonates, remain active in bones for years and can also have a potential teratogenic effect in pregnancy. Because they are designed for a population in which the bone development is no longer physiologically active as it is in younger women, these drugs should mostly be reserved for postmenopausal females and do not have much beneficial value in younger females.

Mechanical stimulation to treat bone loss is another point of discussion that may mimic theimpact of physical activity and so sustain bone density. Pulsed electromagnetic fields have been used in attempts toincrease bone density and vibratory platforms can reduce and possibly prevent bone mass loss. Research in these methods is, however, new.

Perhaps one of the most important interventions in overcoming the female athletic triad is psychological. Changing the competitive mentality in the interest of health and altering the regimen of diet and exercise is key to recovery. Appropriate mental health professionals may be necessary to shift thinking patterns that may be significant barriers to recovery. If the energy deficiency in an athlete is due to intentional calorie restriction, the approach will also be different as compared to when the deficiency is due mostly to excessive calorie expenditure. In the former case, mental health professionals and therapy should be a key component of treatment. Goals of treatment include altering negative beliefs about body image and making regular calorie intake a key concept in enhancing performance. Research has also shown that soccer players with an average body mass index of 21-23 kg/m2 were stronger than those with a lower body mass index. Optimal body mass index may lead to improvements in power in both team sports and those individual sports that are more image conscious.

Patients with the condition may have pre-existing depression or may develop psychological conditions requiring pharmacological treatment. Fluoxetine may be of use in those with disordered eating patterns. Other psychotropic medications may be useful in those with anxiety or depression.

Regular visits with a registered dietician or sports nutritionist also are a key factor in recovery as the athlete’s energy requirement will change progressively. “Training” during recovery should be restricted to the designed training program until recovery, and overtraining or exercise outside of that program should not be allowed. A recovery training program should be designed by the coach on an individual basis. If a personal coach is unavailable, or if the sport consists of a team of runners or players, a physical therapist can take on the role of a temporary personal coach in an outpatient setting.

Prevention

Early detection and prevention is key to recovery. Clues to energy deficits associated with the triad might include declining performance during competitions, mood changes or mood swings, cognitive difficulties, frequent injuries, new fractures, and weight loss. Coaches should be involved in encouraging recovery alongside health care professionals and family members. Expectations for unrealistically low body weight, public or team weigh-ins, and critique from coaches on behalf of athletes should be discouraged.

Conclusion

The female athlete triad, now also known as RED-S, affects both female and male runners and athletes and can become life threatening if it persists and goes unnoticed. Low body mass index, leads to energy deficits that have many consequences which can be long term. A hypo functioning hypothalamic pituitary gonadal axis leads to amenorrhea and low estrogen and follicle stimulating hormone levels in females and decreased testosterone in males. The low hormone levels impact bone density.

Signs or symptoms may include weight loss, amenorrhea or menstrual irregularities, changes in appetite, mood changes, stress fractures, and low energy levels. Pre-participation examinations can be used to screen for the female athletic triad while laboratory testing should be conducted to eliminate other causes of pathophysiology. Laboratory studies may also point out significant electrolyte imbalances, or vitamin deficiencies associated with disordered eating patterns.

Treatment should be multifaceted and coordinated with health care professionals and coaches. A team approach includes collaboration with a primary physician, a coach or physical therapist, a nutritionist, as well as family, friends, and team members. Coaches, family, friends and loved ones must be on the same page when it comes to encouraging the athlete during the recovery process in order to avoid setbacks that may arise from mistrust or lack of confidence in any of the members of the interdisciplinary team treating the athlete. Although there are some pharmacological interventions that may be useful, non-pharmacologic interventions are the first choice. Prevention and early recognition, as well as emphasis on good nutrition, proper rest, and healthy training schedules go a long way in preventing long term consequences associated with the syndrome.